Ann Rheum Dis doi:10.1136/annrheumdis-2011-200802
  • Clinical and epidemiological research
  • Extended report

Comprehensive assessment of rheumatoid arthritis susceptibility loci in a large psoriatic arthritis cohort

Open Access
  1. Anne Barton1
  1. 1Arthritis Research UK Epidemiology Unit, The University of Manchester, Manchester, UK
  2. 2Dermatological Sciences, Salford Royal NHS Foundation Trust, Manchester, UK
  3. 3Section of Musculoskeletal Disease, Leeds Institute of Molecular Medicine, University of Leeds, Leeds, UK
  4. 4Leeds Institute of Molecular Medicine, Musculoskeletal Disease, University of Leeds, Leeds, UK
  5. 5Department of Clinical Medicine, Trinity College Dublin, Dublin, Ireland
  6. 6Department of Rheumatology, Adelaide and Meath Hospital and Trinity College Dublin, Ireland
  7. 7Royal National Hospital for Rheumatic Diseases and Dept Pharmacy and Pharmacology, University of Bath, UK
  8. 8Department of Rheumatology, St. Vincent's University Hospital, Dublin, Ireland
  9. 9Arthritis Research Campaign National Primary Care Centre, Keele University
  1. Correspondence to Anne Barton, The University of Manchester, Arthritis Research UK Epidemiology Unit, Manchester M13 9PT, UK; anne.barton{at}
  1. Contributors AB was responsible for concept and design, initiated the collaborative effort, contributed to interpretation of results, and drafted and revised the final manuscript. She is the guarantor. JB performed data quality control, statistical analysis and interpretation of results, and drafted and revised the final manuscript. He is the guarantor. EF performed laboratory data collection and data quality control. FA was involved in statistical analysis. PH, HM-O, LC, RBW, RM, AWR, DK, EK, NM, OF, JP, AWM and INB were involved in the collaborative effort to collect biological samples. In addition, all authors were also responsible for critically reviewing the draft manuscript and approving the final version.

  • Received 20 September 2011
  • Accepted 30 December 2011
  • Published Online First 10 February 2012


Objective A number of rheumatoid arthritis (RA) susceptibility genes have been identified in recent years. Given the overlap in phenotypic expression of synovial joint inflammation between RA and psoriatic arthritis (PsA), the authors explored whether RA susceptibility genes are also associated with PsA.

Methods 56 single nucleotide polymorphisms (SNPs) mapping to 41 genes previously reported as RA susceptibility loci were selected for investigation. PsA was defined as an inflammatory arthritis associated with psoriasis and subjects were recruited from the UK and Ireland. Genotyping was performed using the Sequenom MassArray platform and frequencies compared with data derived from large UK control collections.

Results Significant evidence for association with susceptibility to PsA was found toa SNP mapping to the REL (rs13017599, ptrend=5.2×104) gene, while nominal evidence for association (ptrend<0.05) was found to seven other loci including PLCL2 (rs4535211, p=1.7×10−3); STAT4 (rs10181656, p=3.0×10−3) and the AFF3, CD28, CCL21, IL2 and KIF5A loci. Interestingly, three SNPs demonstrated opposite effects to those reported for RA.

Conclusions The REL gene, a key modulator of the NFκB pathway, is associated with PsA but the allele conferring risk to RA is protective in PsA suggesting that there are fundamental differences in the aetiological mechanisms underlying these two types of inflammatory arthritis.


  • Funding This work is supported by Arthritis Research UK.

  • Competing interests None.

  • Ethics approval North West Multicentre Research Ethics Committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.

This paper is freely available online under the BMJ Journals unlocked scheme, see